Small biological detectors using quartz mass sensing currently are commercially implemented using low frequency (˜10 MHz) quartz resonators on macro-size substrates mounted on plastic disposable cartridges for biological sample exposure and electrical activation.
Previous quartz resonators used in biological analysis have utilized flat quartz substrates with electrodes deposited on opposite sides of the quartz for shear mode operation in liquids. In order for the substrates not to break during fabrication and assembly, the quartz substrate needs to be of the order of 100 microns thick. This sets a frequency limit for the resonator of roughly ˜20 MHz since the frequency is inversely proportional to the thickness.
Chemically etching inverted mesas has been used to produce higher frequency resonators, but this usually produces etch pits in the quartz that can result in a porous resonator which is not suitable for liquid isolation.
However, it is well known that the relative frequency shift for quartz sensors for a given increase in the mass per unit area is proportional to the resonant frequency as given by the Sauerbrey equation. Therefore, it is desirable to operate the sensor at a high frequency (UHF) and thus use ultra-thin substrates that have not been chemically etched.
It is also desirable to minimize the diffusion path length in the analyte solution to the sensor surface to minimize the reaction time needed to acquire a given increase in the mass per unit area. Thus, the dimension of the flow cell around the sensor in the direction perpendicular to the sensor should be minimized. Currently, this dimension is determined by the physical thickness of adhesive tape (WO 2006/103439 A2) and is of the order of 85 microns. It is desirable not to increase this dimension when implementing a higher frequency resonator. In addition, the alignment of tape and the quartz resonators can be difficult and unreliable thereby causing operational variations.
Current UHF quartz MEMS resonators fabricated for integration with electronics (see U.S. Pat. No. 7,237,315) can not be used in commercial low cost sensor cartridges since one metal electrode can not be isolated in a liquid from the other electrode and electrical connections can not be made outside the liquid environment.
Commercial quartz resonators are formed by lapping and polishing small 1-2 inch quartz substrates to approximately the proper frequency and then chemically etching away the unwanted quartz between the resonators. Chemical etching is also used to fine tune the frequencies and to etch inverted mesas for higher frequency operation. However, as stated above, handling and cracking issues usually dictate that the lapped and polished thicknesses are of the order of 100 microns, and chemically etching deep inverted mesas produces etch pits which significantly reduce the yield and can result in a porous resonator. This invention suggests utilizing the previously disclosed (see U.S. Pat. No. 7,237,315 mentioned above) handle wafer technology for handling large thin quartz substrates for high frequency operation plus double inverted mesa technology using dry etching for providing high frequency non-porous resonators with (1) a thick frame for minimizing mounting stress changes in the resonator frequencies once a flow cell is formed, (2) a thin flow cell for reducing the sensor reaction time, and (3) quartz through wafer vias for isolating the active electrodes and electrical interconnects from the flow cell. Since, to the inventor's understanding, commercial manufacturers do not use quartz plasma etching for defining thin non-porous membranes nor quartz through-wafer vias for conventional packaging, the current fabrication and structure would not be obvious to one skilled in the art familiar with this conventional technology.
There is a need for even smaller biological detectors, which can effectively work with even smaller sample volumes yet having even greater sensitivity than prior art detectors.